Breast cancer stands as a formidable adversary in the global fight against malignancies. The heterogeneity of its pathology presents both challenges and opportunities. Its diverse clinicopathological manifestations emphasize the paramount need for refining diagnostic and prognostic tools to aid clinicians in tailoring treatment modalities to individual patient profiles, thereby ensuring optimized therapeutic outcomes[1]. Our study concentrated on the potential of PIBF1 as such a marker.
Initially distinguished in pregnancy immunology, the PIBF1 transition to oncology research appeared surprising at first glance. However, its increased expression in various cancers compared with their normal tissue adds credence to its potential role in tumor progression and possibly in treatment modulation. The focal point of our study was to unravel the relevance of PIBF1 and its characteristics in the breast cancer panorama. Given the inherent chromosomal significance of its gene location and elevated expression in breast cancer cells, this protein has emerged as another probable keystone in breast cancer pathophysiology[2, 4, 9].
The immune modulatory role of PIBF1, coupled with its interplay in cellular events such as proliferation and apoptosis, underpins its importance in tumorigenesis[2, 3]. Although its exact mechanisms remain under exploration, preliminary findings from other malignancies set a promising stage for its implications in breast cancer[7, 8, 10].
In our study, garnered from a sizable patient cohort, some insights were highlighted in PIBF1 and breast cancer. In the analysis of clinicopathological features, patients expressing PIBF1 exhibited an association with lower histologic and nuclear grade compared with those without PIBF1 expression. Additionally, PIBF1 expression was concurrently associated with a decrease in Ki-67 compared to the PIBF1-negative cohort. This pattern was accentuated within the non-TNBC cohort when categorizing patients into TNBC and non-TNBC subsets. Such findings underscore that PIBF1 expression potentially indicates more favorable clinicopathological attributes within breast cancer pathophysiology.
Additionally, PIBF1 expression was correlated with hormone receptor positivity, suggesting that its expression is not only associated with favorable prognostic indicators but may also be intrinsically linked to hormone-related characteristics of the cancer (Tables 2, 3). Within this study cohort, a quantitative evaluation was conducted on the relationship between the ER Allred score and PIBF1 expression, revealing a positive correlation. These findings potentially underscore the hormone-related nature of PIBF1, warranting more extensive research to fully elucidate this aspect.
In the survival analysis, the overall patient population showed enhanced OS with PIBF1 expression, reaching statistical significance (p = 0.010). Upon stratification into TNBC and non-TNBC subsets, the statistically significant improvement in survival was exclusively observed within the non-TNBC cohort (p = 0.013). Subsequent multivariable analysis concerning OS within the non-TNBC cohort indicated that PIBF1 expression might correlate with a reduced risk of adverse outcomes. While this association approached statistical significance, it did not conclusively attain it (hazard ratio = 0.44, 95% confidence interval = 0.18–1.11, p = 0.082). However, these associations may vary with the expansion of the study cohort to include a larger patient population. The survival analysis unveiled compelling distinctions predicated on PIBF1 expression, particularly prominent in the non-TNBC cohort. Collectively, our findings indicate that PIBF1 expression is favorably related to survival outcomes among patients with high-risk breast cancer who have been administered chemotherapy.
Perhaps one of the most enlightening aspects of this study was the exploration of PIBF in the context of taxane-based chemotherapy. With all patients in our cohort being subjected to this regimen, discerning a potential correlation with PIBF1 was paramount. Our in vitro assays, including viability and clonogenic assessments, revealed differential responses based on PIBF1 expression. Upon paclitaxel administration, the significant reductions in cell viability and colony formation in high-PIBF1-expressing cell lines, such as BT-549 and BT20, mirrored the inherent biology observed in the patient cohort. Moreover, our genetic knockdown experiments further reinforced the influence of PIBF1 on chemotherapy sensitivity.
Kim et al.[11] identified that the larger isoform of PIBF1, primarily associated with the centrosome, functions as a pericentriolar satellite protein for the integrity of the mitotic spindle pole and have named this protein CEP90. Taxanes inhibit the dynamic behavior of microtubules, leading to the induction of multipolar mitotic spindles and the redistribution of the microtubule network from the centrosomes to the cell cortex[12]. Given the impact of PIBF1 on spindle pole conformation, it may exert a synergistic effect with taxane-based chemotherapy. This interaction could hypothetically contribute to the observed enhancement in the chemotherapy response and outcomes evidenced in the study.
In an era of personalized medicine, with the diverse treatment approaches in breast cancer, the identification and validation of markers like PIBF1 could facilitate more tailored and individualized therapeutic strategies. This aligns with the overarching goal of optimizing patient outcomes in the complex landscape of breast cancer treatment.
Our study establishes a preliminary but robust foundation for PIBF1's significance in breast cancer prognosis and treatment strategies. However, this study had some limitations, primarily hinged on its retrospective nature and single-center design. Furthermore, given that the cohort predominantly consisted of high-risk patients who had received chemotherapy, there are inherent limitations in extrapolating the natural attributes of PIBF1 to the broader breast cancer population. Further investigation warranted to elucidate the oncogenic mechanisms of PIBF1 and its impact on patients, including those who have not received chemotherapy and those treated with other therapeutic modalities.